Scientists Parse Genes Of Breast Cancer's Four Major Types

Scientists say a new report in the journal Nature provides a big leap in the understanding of how different types of breast cancer differ.

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Originally published on November 28, 2012 10:46 am

Scientists have known for a while that breast cancer is really four different diseases, with subtypes among them, an insight that has helped improve treatment for some women.

But experts haven't understood much about how these four types differ. A new report, published online in the journal Nature, provides a big leap in that understanding.

"This paper gives us a level of detailed knowledge of breast cancer that vastly exceeds what was available before," says Matthew Meyerson, one of the paper's 348 authors. The effort is part of The Cancer Genome Atlas network, funded by the National Institutes of Health.

Meyerson and his colleagues used a half-dozen different types of analysis to comb through the genes of 825 breast cancer patients.

"We basically studied the genomes of breast cancers from each of these women in comparison to the genomes of the rest of their bodies," Meyerson told Shots.

They found 40 or so key differences in the genes among the four major types of breast cancer. The types are basal-like (also called triple-negative), luminal A, luminal B and HER2-enriched.

All of these differences are potential targets for cleverly designed drugs.

Some of the similarities between breast cancer and other types of cancer may also be important clues. For instance, the researchers found that certain mutations may underlie basal-like breast cancer and ovarian cancer, especially in women who inherit a BRCA-1 or BRCA-2 mutation.

So some think it might be reasonable to try ovarian cancer drugs in breast cancer patients with these genetic markers.

But Meyerson, who's with the Dana Farber Cancer Institute in Boston and the Broad Institute across the river in Cambridge, Mass., cautions that all of this is a long way from the outmoded dream of a silver bullet that would knock out breast cancer — or any other kind.

"I think in the end, to treat cancer, we're going to be developing a lot of specific silver bullets, but we'll need to use them in combination," he says. "So you'll really need a gold bullet and a silver bullet and a bronze bullet altogether to effectively treat cancers."

Charles Perou of the University of North Carolina, the first author on the paper, says that arsenal is being developed.

"The bad news is that it's complicated. And we have to figure out which bullet is to be used, where and when," he says. "That has to be done in rigorous clinical trials. And that is happening."

But consumer advocates caution that it's going to take a long time to find and test all these different "bullets."

"For me, I have to say, my enthusiasm around this as new and exciting is dampened by the knowledge that it's going to be many, many, many years before we see something that is clinically meaningful for patients," Karuna Jaggar of Breast Cancer Action told Shots. "In the meantime, too many women continue to be diagnosed with the disease."

Fran Visco, president of the National Breast Cancer Coalition, agrees.

"Finding targets, doing ... genomic screening, that's not the end goal," she says. "That is simply a tool, a step on the way to figuring out how to save lives.

"We have to be careful what we celebrate," Visco adds. "And we have to be careful what we consider to be a success. We are nowhere near success."

Perou says he understands their frustration.

"We're all — including myself — disappointed in the speed required to make these clinical advances," he says. "It's far easier to make a discovery than it is to translate that discovery into a clinical impact."

Perou thinks "optimistically" that the first impact from this new research could be two to five years away. It might be for the most common type — luminal breast cancer. That's because, the new paper shows, it has relatively few genetic mutations.

Unexpectedly, the researchers found that virtually all women with luminal-A breast cancers have a mutation in a cell receptor called phosphoinositide 3-kinase. There are already drugs in the works that target PI3-kinases.

Copyright 2012 National Public Radio. To see more, visit http://www.npr.org/.

Transcript

MELISSA BLOCK, HOST:

Now, some encouraging news about breast cancer. Scientists have pinpointed dozens of genetic mutations behind the four major types of the disease. Breast cancer kills nearly 40,000 American women each year. While researchers say no one should expect any overnight successes, these findings do give them many more ways to attack the disease with drugs. NPR's Richard Knox reports.

RICHARD KNOX, BYLINE: For at least a decade, experts have known breast cancer is really four different diseases. And that's helped improve treatment for some. But scientists haven't understood much about how these four types differ. The new report, published online by the journal Nature, is a big leap in that understanding.

MATTHEW MEYERSON: This paper gives us a level of detailed knowledge of breast cancer that vastly exceeds what was available before.

KNOX: That's Matthew Meyerson, one of the paper's 348 authors. He and his colleagues analyzed the genes from more than 800 breast cancer patients.

MEYERSON: We basically studied the genomes of the breast cancers from each of these women in comparison to the genomes of the rest of their bodies.

KNOX: They found 40 or so key differences in the genes among the four major types of breast cancer. All of these differences are potential targets for cleverly designed drugs. But Meyerson, who's with Dana Farber Cancer Institute in Boston, cautions it's a long way from the outmoded dream of coming up with a silver bullet that would knock out breast cancer or any other kind.

MEYERSON: I think in the end, to treat cancer we're going to be developing a lot of specific silver bullets, but we'll need to use them in combination. So you'll really need a gold bullet, and a silver bullet and a bronze bullet all together to effectively treat cancers.

CHARLES PEROU: And that arsenal is being developed, which is the good news, right?

KNOX: That's Charles Perou of the University of North Carolina, another study author.

PEROU: But the bad news is it's complicated. And we have to figure out, you know, which bullet to use, when and where, and that needs to be done in rigorous clinical trials and that is happening.

KNOX: But it's going to take a long time to find and test all those different bullets, says Karuna Jaggar of Breast Cancer Action, a consumer group.

KARUNA JAGGAR: For me, I have to say, my enthusiasm around this as new and exciting is somewhat dampened by the knowledge that it's going to many, many, many years before we see something that is clinically meaningful for patients. And in the meantime, too many women continue to be diagnosed with the disease.

KNOX: Fran Visco agrees.

FRAN VISCO: Finding targets, doing screening, genomic screening, that's not the end goal. That is simply a tool, a step in the way to figuring out how to save lives.

KNOX: She's president of the National Breast Cancer Coalition, another advocacy group.

VISCO: We have to be careful what we celebrate and we have to be careful what we consider to be success. We are nowhere near a success.

KNOX: Perou, the North Carolina researcher, understands their frustration.

PEROU: We're all, including myself, right, disappointed in the speed required to make these clinical advancements. It's far easier to make a discovery than it is to translate that discovery into a clinical impact.

KNOX: He thinks the first impact from this new research could be two to five years away. That would probably be for the most common type called luminal breast cancer. And that's because, the new paper shows, it has relatively few genetic mutations and there's already a drug in the works for one of them. Richard Knox, NPR News. Transcript provided by NPR, Copyright National Public Radio.